Arthritic disorders are the second leading cause of losses in time and earnings in the United States. Approximately six million of all arthritis sufferers are afflicted rheumatoid arthritis. Of these, over fifty percent (50%) ultimately will have involvement of the knee joint, over eighty percent (80%) will involve the hand joint and somewhat smaller percentages will have involvement of other joints such as the ankle, elbow and shoulder.
Rheumatoid arthritis is believed to be an autoimmune disease wherein parts of the body are attacked by antibodies manufactured in the body. These antibodies may be produced in response to viruses present in the body. While the mechanism for rheumatoid arthritis is not defined, it is a systemic disease. When the disease is active, the erythrocyte sedimentation rate (ESR) is elevated and the blood tests positive for rheumatoid factor.
A source of disability for the sufferer of rheumatoid arthritis is an inflammatory response, of unknown origin, in the synovium, or lining, of the afflicted joint. This chronic inflammation, or synovitis, leads to pannus formation and, eventually, destruction of the joint cartilage.
Presently, the primary method of treating rheumatoid arthritis is by use of compounds directed at blocking the inflammatory process. These compounds include aspirin, penicillamine, gold salts and many other ethical drugs. Unfortunately, these attempts are often unsuccessful and the relief provided is temporary at best. In such instances, the primary alternative is the surgical excision of the inflamed synovium in a procedure known as surgical synovectomy. In this procedure the abnormal synovium and pannus formation are surgically removed. While, in many cases, this procedure proves to arrest the disease, it also has a significant number of drawbacks and limitations. Among these are limitations on complete removal of the inflamed synovium, the risks and dangers inherent in the operation itself; and the required lengthy recovery period, much of which is spent in the hospital.
In order to overcome these problems, attempts have been made to destroy the diseased synovium by the performance of a procedure known as radiation synovectomy. Intra-articular injection of colloidial gold-198 (.sup.198 Au) has been reported to abate inflamed synovium (Fellinger et al, 33 WEIN Z. INN, Med. 351, (1952) and Ansell et al, 22 Ann. Rheum. Dis. 435 (1963)). Unfortunately, this procedure is disadvantageous due to the small particle size of the gold colloid utilized and the high energy gamma photons emitted during decay (gamma emission). This emission poses dangers to the patient by increasing the whole body dose, thereby exposing healthy tissue to radiation, and posing substantial difficulties with radiation protection for hospital personnel.
The use of other radionuclides has also been attempted in radiation synovectomy. These radionuclides include Erbium-169 (.sup.169 Er) as reported in Menkes et al, 36 Ann. Rheum. Dis. 254 (1977); Rhenium-186 (.sup.186 Re) as reported in Deckart et al, 3 Radiobiol, Radiother 363 (1979) and in DelBarre et al, 2 Nouv. Presse. Med 1372 (1973); Phosphorus-32 (.sup.32 P) as reported in Wenston et al, 14 J. Nuc. Med 886 (1973), and Yttrium-90 (.sup.90 Y) as reported in Gumpel et al, 48 Br. J. Radiol. 377 (1975).
Each of these radionuclides (.sup.169 Er, .sup.186 Re, .sup.32 P, .sup.198 Au and .sup.90 Y) has proven disadvantageous due to either the long physical half-life of the particular radionuclide involved, the small particle size of the system, and/or the occurrence of significant amounts of radioactivity leaking from the affected joints and associated chromosonal aberrations in the lymphocytes of the patient. (See also; Oka et al, 17 Acta Rheum. Scand. 148 (1971) and Virkkunen et al, 13 Acta Rheum, Scand, 1967.)
Currently, the preferred radionuclide in the prior art is Dysprosium.sup.165 (Dy.sup.165) hyrdroxide in Ferric Hydroxide. Sledge et al, 182 Clin. Ortho, and Rel. Research 37 (1984) (hereinafter referred to as "Sledge"). Sledge has found that the use of .sup.165 Dy hydroxide in ferric hydroxide is more advantageous in performing radiation synovectomy than the aforementioned radionuclides. Sledge has identified as the advantages of .sup.165 Dy hydroxide in ferric hydroxide: (1) proper energy range beta emissions; (2) formation of a larger colloid which reduces the potential of leakage; and (3) an extremely short half-life of 2.3 hours which further reduces the effects of potential leakage.
These are qualities which the prior art has reported to be desirable when selecting an appropriate radioactive compound for use in radiation synovectomy (See also Sledge et al, 20 Arthritis Rheum 1334 (1977), Noble, et al, 65A J. Bone Joint Surg. 381 (1983), and Deckert and Gumpel, both supra).
While the short half-life of .sup.165 Dy in ferric hydroxide is one of the major characteristics noted by Sledge and the other references which make it such a desirable candidate for radiation synovectomy, this short half-life also proves to be a major limitation to its use. .sup.165 Dy requires a nuclear reactor in order to be produced. It also must be injected within a few hours of its manufacture to be effective. As a result, its utility in radiation synovectomy is severely limited by geographical and distribution factors.
Accordingly, it is obvious that there remains a need for an effective radioactive compound that will have both utility in radiation synovectomy and will be able to be prepared in, and distributed from, a central location using existing transportation channels.